J Toxicol Environ Health A 1998 Jun 26;544:319-33. doi: 10.1080/009841098158872.

Chlorpropham [isopropyl N-(3-chlorophenyl) carbamate] disrupts microtubule organization, cell division, and early development of sea urchin embryos.

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The herbicide CIPC [N-(3-chlorophenyl) carbamate] has been shown to disrupt microtubule organization in plants, apparently by interfering with the functioning of the microtubule organizing center. Very few studies have examined the effects of CIPC on animal cell microtubules and centrosomes, however, and the effects of this cytoskeletal disrupting agent on fertilization and early development have not been studied in detail. To address these questions, fertilized sea urchin eggs were cultured in the presence of CIPC until the prism stage, and perturbations in the cytoskeleton and development were examined. It was found that Lytechinus pictus embryos are sensitive to micromolar amounts of CIPC, and that a characteristic set of cytoskeletal and developmental deficits is produced as a result of exposure to this herbicide. Mitotic spindles were truncated and randomly oriented within zygotes and blastomeres, and cytokinesis was compromised, resulting in the production of blastomeres of various sizes and ploidy. Interestingly, in spite of these cytoskeletal and nuclear alterations, spindle poles at fourth cleavage retained their ability to interact with the plasma membrane in a manner similar to that normally characterizing the unequal division of macromeres and micromeres. CIPC treatment resulted in unequal cell divisions at atypical times, and skeletal spicule formation in these embryos was abnormal. These results indicate that CIPC may pose a significant health risk during mammalian embryogenesis; in addition, it may be a useful tool with which to study microtubule and centrosomal functioning during animal cell division-especially in those cell types that exhibit stereotypic patterns of cell division during early development.

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Genes referenced: LOC100887844 LOC115919910 LOC583082